Dosage of Avapritinib

Recommended Administration

Avapritinib should be taken orally on an empty stomach, at least 1 hour before a meal or 2 hours after a meal.

If a dose is missed, it should be taken within 8 hours before the next scheduled dose.

If vomiting occurs after taking the medication, no additional dose is needed; the next dose should be taken at the originally planned time.

GIST Harboring PDGFRA Exon 18 Mutations

Patients selected for avapritinib treatment based on the presence of PDGFRA exon 18 mutations. Currently, there is no FDA-approved test for detecting exon 18 mutations.

The recommended dose of avapritinib for GIST patients is 300 mg, taken orally once daily. Treatment should be continued until disease progression or the occurrence of unacceptable toxicity.

Advanced Systemic Mastocytosis (AdvSM)

The recommended dose of avapritinib for AdvSM patients is 200 mg, taken orally once daily. Treatment should be continued until disease progression or the occurrence of unacceptable toxicity.

Indolent Systemic Mastocytosis (ISM)

The recommended dose of avapritinib for ISM patients is 25 mg, taken orally once daily.

Dose Adjustment for Adverse Reactions

Recommended dose reductions and adjustments for adverse reactions are as follows:

Recommended Dose Reductions:For GIST patients:

First dose reduction: to 200 mg once daily;

Second dose reduction: to 100 mg once daily.

GIST patients who cannot tolerate the 100 mg once-daily dose should permanently discontinue avapritinib.

For AdvSM patients:

First dose reduction: to 100 mg once daily;

Second dose reduction: to 50 mg once daily;

Third dose reduction: to 25 mg once daily.

AdvSM patients who cannot tolerate the 25 mg once-daily dose should permanently discontinue avapritinib.

Recommended Dose Adjustments:For GIST or AdvSM patients:

Intracranial hemorrhage: Any grade, permanently discontinue avapritinib.

Cognitive effects:

Grade 1: Continue avapritinib at the same dose or a reduced dose, or suspend treatment until improvement to baseline or resolution. Then resume treatment at the same dose or a reduced dose.

Grade 2 or 3: Suspend avapritinib until improvement to baseline, Grade 1, or resolution. Then resume treatment at the same dose or a reduced dose.

Grade 4: Permanently discontinue avapritinib.

Other adverse reactions: Grade 3 or 4, suspend avapritinib until improvement to ≤ Grade 2. Then resume treatment at the same dose or a reduced dose based on clinical conditions.

For AdvSM patients:

Thrombocytopenia: When the platelet count is below 50×10^9/L, interrupt avapritinib treatment until the platelet count recovers to ≥50×10^9/L, then resume treatment at a reduced dose. If the platelet count fails to recover above 50×10^9/L, consider platelet support.

Concomitant Use with Strong or Moderate CYP3A Inhibitors

Concomitant use of avapritinib with strong or moderate CYP3A inhibitors should be avoided. If concomitant use with a moderate CYP3A inhibitor cannot be avoided, the starting dose of avapritinib should be adjusted to:

100 mg once daily orally for GIST patients;

50 mg once daily orally for AdvSM patients.

For ISM patients, concomitant use of avapritinib with strong or moderate CYP3A inhibitors should be avoided.

Dose Adjustment for Severe Hepatic Impairment

For patients with severe hepatic impairment, the recommended starting dose of avapritinib should be adjusted to:

200 mg once daily orally for GIST patients;

100 mg once daily orally for AdvSM patients;

25 mg every other day orally for ISM patients.

FDA，2024.11